29 Jul 2016

‘Retraining’ the immune system of patients with allergies

Professor Robyn O'Hehirgives an overview of her research into immune system components involved in reducing allergic response.

Turning off the T cells in allergy

An aberrant allergic (IgE) response to a usually harmless stimulus (allergen) is orchestrated by a population of white blood cells known as helper T cells. By reining in the activities of these T cells, it is possible to reduce the severity of the allergy.

Professor Robyn O’Hehir initiated this stream of research at St Mary’s Hospital Medical School in London in the early nineties. Since returning to Australia, Prof O’Hehir together with Emeritus Prof Jennifer Rolland applied this approach for a number of important allergens associated with human disease (grass pollens, latex and peanut), as knowing these key instigators or “T cell epitopes” is a vital step in understanding allergies and is important in the development of new methods to switch off allergies by ‘retraining’ the immune system of patients with allergies.

Tolerance in human T cells?

Could an allergen T cell epitope invoke allergen non-responsiveness in humans? To test this idea, the Allergy Laboratory researchers first needed to define the critical allergens and T cell epitopes most frequently recognised by patients’ T cells in allergy. Many of the sequences of major allergen proteins have been identified by the Monash/Alfred team or others and this information helped design short pieces of proteins to identify those which most frequently stimulated allergy in the laboratory.

These ‘dominant’ T cell epitopes have been the focus of further studies where sets of small protein pieces were developed as “candidate vaccines” to safely induce clinical and immunological tolerance to house dust mite, then grass pollens and more recently, peanuts.

Dr Sara Prickett joined the Allergy Laboratory in 2007 and after strong laboratory efforts from her and the Allergy Team a peanut Synthetic Peptide ImmunoRegulatory Epitope (SPIRE) therapy is moving through obligatory toxicology and pharmacokinetics studies currently with planned rapid escalation to early phase clinical trials.
.A “tolerising” vaccine for peanut allergy?

Currently, “allergy shots” (or allergen immunotherapy) are an option to treat people with bee sting allergy or severe hay fever. The allergen extracts are injected in increasing amounts to induce tolerance, preventing allergy next spring or with the next bee sting.

An attraction of the approach using short allergen peptides is that careful selection can avoid the portion that binds IgE; hence avoiding adverse effects. So, although the technique is an old one, using the more scientific approach should in the long run provide more rational and safer treatments.

Clinical trials haven’t started yet in peanut allergy but there are very encouraging trials in house dust mite allergy and seasonal hayfever. The house dust mite treatments include Professor O’Hehir’s identified T cell epitopes from the 1990s and the hayfever studies include T cell epitopes identified by the O’Hehir and Rolland Monash/Alfred Team in more recent years. Profs O’Hehir and Rolland and Dr Prickett are confident that a peanut vaccine holds great opportunity for success.